Genetic analysis of the novel SARS-CoV-2 host receptor TMPRSS2 in different populations

  1. Roberta Russo
  2. Immacolata Andolfo
  3. Vito Alessandro Lasorsa
  4. Achille Iolascon
  5. Mario Capasso

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Abstract

The infection coronavirus disease 2019 (COVID-19) is caused by a virus classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At cellular level, virus infection initiates with binding of viral particles to the host surface cellular receptor angiotensin converting enzyme 2 (ACE2). SARS-CoV-2 engages ACE2 as the entry receptor and employs the cellular serine protease 2 (TMPRSS2) for S protein priming. TMPRSS2 activity is essential for viral spread and pathogenesis in the infected host. Understanding how TMPRSS2 protein expression in the lung varies in the population could reveal important insights into differential susceptibility to influenza and coronavirus infections. Here, we systematically analyzed coding-region variants in TMPRSS2 and the eQTL variants, which may affect the gene expression, to compare the genomic characteristics of TMPRSS2 among different populations. Our findings suggest that the lung-specific eQTL variants may confer different susceptibility or response to SARS-CoV-2 infection from different populations under the similar conditions. In particular, we found that the eQTL variant rs35074065 is associated with high expression of TMPRSS2 but with a low expression of the interferon (IFN)-α/β-inducible gene, MX1 , splicing isoform. Thus, these subjects could account for a more susceptibility either to viral infection or to a decrease in cellular antiviral response.

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  1. ScreenIT

    SciScore for 10.1101/2020.04.23.057190: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The variants in TMPRSS2 gene region (chr21:42836478-42903043, 66.566 Kb) were obtained from the gnomAD v2.1.1 database.
    gnomAD
    suggested: (Genome Aggregation Database, RRID:SCR_014964)
    Annotation of TMPRSS2 variants and eQTLs was performed with ANNOVAR by using the pathogenicity prediction tools described in Supplementary Table S1 and the allele frequencies of human populations reported in Supplementary Table S5.
    ANNOVAR
    suggested: (ANNOVAR, RRID:SCR_012821)
    , CADD v1.3 (Phred score >15) for the pathogenic variants.
    Phred
    suggested: (Phred, RRID:SCR_001017)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.04.23.057190 on bioRxiv